Tiopronin
(Synonyms: BRN 1859822, (±)-Tiopronin) 目录号 : GC40555
Tiopronin is an antioxidant that has diverse biological activities.
Cas No.:1953-02-2
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Tiopronin is an antioxidant that has diverse biological activities. It reduces free radical production by murine macrophages and granulocytes in vitro in a dose-dependent manner. Tiopronin induces expression of hypoxia-inducible factor 1α (HIF-1α) and increases VEGF secretion in human colon carcinoma cells. Rectal administration (500 μL of a 10 mM solution) reduces myeloperoxidase activity and reduces pro-inflammatory cytokine production in the colon in a rat model of colitis. Tiopronin (80-320 mg/kg per day) reduces the incidence of cleft palate in fetuses born to female mice treated with teratogenic methylmercury chloride. Tiopronin (100 mg/kg) reduces heme oxygenase 1 mRNA expression, lipid peroxidation, and transverse aortic constriction in a mouse model of cardiac hypertrophy. Tiopronin (20 mg/kg) is hepatoprotective, increasing activity of the antioxidant enzymes superoxide dismutase and glutathione peroxidase and reversing hepatocyte degeneration in a rat model of high-fat diet-induced non-alcoholic steatohepatitis.
| Cas No. | 1953-02-2 | SDF | |
| 别名 | BRN 1859822, (±)-Tiopronin | ||
| Canonical SMILES | OC(CNC(C(S)C)=O)=O | ||
| 分子式 | C5H9NO3S | 分子量 | 163.2 |
| 溶解度 | Water : 100 mg/mL (612.78 mM; Need ultrasonic) DMSO : ≥ 100 mg/mL (612.78 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 6.1275 mL | 30.6373 mL | 61.2745 mL |
| 5 mM | 1.2255 mL | 6.1275 mL | 12.2549 mL |
| 10 mM | 0.6127 mL | 3.0637 mL | 6.1275 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Pharmacokinetics of oral Tiopronin
Eur J Clin Pharmacol 1993;45(1):79-84.PMID:8405034DOI:10.1007/BF00315354.
Ten healthy subjects were given 500 mg (3064 mumol) Tiopronin, or 2-mercaptopropionylglycine (2-MPG) by mouth. Cmax was reached after 3-6 h, and after a shorter beta-phase a long terminal half-life of 53 h of total Tiopronin was found. Tiopronin measured as unbound (non-protein-bound) drug disappeared more rapidly from plasma, with a calculated t1/2 of 1.8 h. Mean residence time was higher (58 h) when calculated as total Tiopronin than as unbound Tiopronin (6 h), and this was also the case for the volume of distribution (V lambda = 455 l vs V lambda,u = 41 l). The results indicate extensive protein binding in plasma and a deep pool of tissue bound Tiopronin after the first absorption and distribution phases. Absolute bioavailability (f) was 63%, and bioavailability calculated from urinary excretion was 47%, which are well correlated with each other. Urinary excretion was mainly confined to the first 6 h (74%) and was almost complete (98%) within 12 h. We conclude that the maximal absorption of the Tiopronin was late, protein and tissue binding of the drug were high and its bioavailability varied. The renal excretion of low molecular weight Tiopronin occurred early, which implies that the drug should be given in divided doses, at least twice daily, for optimal efficiency in the treatment of cystinuria.
Influence of Tiopronin on the Metabolism of Alcohol in Healthy Subjects
Drug Res (Stuttg) 2017 Apr;67(4):204-210.PMID:28142160DOI:10.1055/s-0042-123826.
Drug safety- and drug-alcohol interaction studies have mainly been conducted for frequently prescribed drugs with high financial interests. Orphan drugs such as Tiopronin (ORPHA25073) are often neglected in terms of clinical research. Tiopronin is a drug that is mainly used for the treatment of cystinuria. In this study, the interaction of Tiopronin regarding the metabolism of alcohol (primary objective), and the safety of Tiopronin in combination with alcohol was tested in healthy volunteers.In this randomised, double-blind, cross-over study, 13 healthy subjects received 500 mg Tiopronin or an identical looking placebo 1 h before the intake of 0.8 g of alcohol per kg of bodyweight. Blood alcohol concentrations were measured over the course of 12 h after consumption. The experiment was repeated 7 days later with the previous placebo group receiving the active drug and vice-versa. Changes in blood alcohol AUC and elimination rate k were analysed using a 2-tailed t-test. Further acetaldehyde concentrations were measured. Additionally, the concentration ability of the subjects was tested and any adverse effects were recorded.There was no significant change in blood alcohol or acetaldehyde concentration. Significant differences in concentration tests refer presumably to learning effects. No serious adverse event occurred. All adverse events were reversible and there was no significant difference in occurrence between drug and placebo group.It was demonstrated that Tiopronin does not affect the metabolism of alcohol. Intake of Tiopronin in combination with alcohol has no safety implications on healthy subjects.
Dentine collagen cross-linking using tiopronin-protected Au/EDC nanoparticles formulations
Dent Mater 2019 Jul;35(7):1017-1030.PMID:31064669DOI:10.1016/j.dental.2019.04.005.
Objective: The aim of this study was to investigate EDC-assisted collagen crosslinking effect with different concentrations of tiopronin-protected gold (TPAu) nanoparticles on demineralized dentine. Methods: TPAu nanoparticles were fabricated from 0.31-g tetrachloroauric acid and 0.38-g of N-(2-mercaptopropionyl) glycine (2.4-mmol). Then co-dissolved using 35-mL of 6:1 methanol/acetic acid and mixed using NaBH4. EDC (0.3-M) was conjugated to TPAu nanoparticles at TPAU/EDC-0.25:1, and TPAU/EDC-0.5:1 treatment formulations ratios. Dentin specimens treated with 0.3-M EDC solution alone or left untreated were used as control. Nanoparticles formulations were characterized in term of particles morphology and size, Zeta potential, thermogravimetric analysis and small-angle X-ray scattering. Dentin substrates were characterized in term of TEM investigation, dentin proteases characterization, hydroxyproline liberation, elastic modulus measurement, Raman analysis and confocal microscopy viewing. Results: TEM evaluation of Tiopronin protected gold nanoparticles dispersion revealed nano-clusters formations in both groups. However, based on our TEM measurements, the particle-size was ranging from ˜20 to 50 nm with spherical core-shape which were almost similar for both TPAu/EDC ratios (0.5:1 and 0.25:1). Zeta potential measurements indicate negative nanoparticles surface charge. SAXS profiles for both formulations, suggest a typical profile for uni-lamellar nanoparticles. Superior dentin collagen cross-linking effect was found with the TPAu/EDC nanoparticles formulations compared to the control and EDC treated groups. Significance: Cross-linking of dentin collagen using TPAu coupled with EDC through TPAu/EDC nanoparticles formulations is of potential significance in improving the biodegradation resistance, proteases inhibition, mechanical and structural stability of demineralized dentin substrates. In addition, the cross-linking effect is dependent on TPAu/EDC ratio, whereas higher cross-linking effect was found at TPAu/EDC ratio of 0.5:1.
Kinetics and mechanism of reactions of the drug Tiopronin with platinum(IV) complexes
J Inorg Biochem 2013 Aug;125:9-15.PMID:23665090DOI:10.1016/j.jinorgbio.2013.04.003.
Tiopronin, a synthetic thiol-containing drug being used in treatments of cystinuria and certain types of rare arthritis, is also a hepatoprotective and a detoxifying agent. Many analytical methods have been developed based on its redox chemistry with metal ions/complexes, but the kinetic and mechanistic aspects are poorly understood. In this work, the oxidation of Tiopronin by cisplatin prodrug and a model compound, cis-[Pt(NH3)2Cl4] and trans-[PtCl2(CN)4](2-), was investigated. The oxidation kinetics was followed by a stopped-flow spectrophotometer over a wide pH range under the pseudo first-order conditions of [Tiopronin]≫[Pt(IV)]. Time-resolved spectra were also recorded for both Pt(IV) complexes, enabling to establish an overall second-order rate law: -d[Pt(IV)]/dt=k'[Tiopronin][Pt(IV)], where k' pertains to observed second-order rate constants. Under the kinetic conditions, Tiopronin was oxidized to form the tiopronin-disulfide exclusively as identified by mass spectrometry. A reaction mechanism was proposed, involving parallel reductions of the Pt(IV) complexes by the three protolytic Tiopronin species as rate-determining steps. The rate constants for the rate-determining steps were derived. The fully deprotonated Tiopronin is about 4×10(4) more reactive than its corresponding thiol form for both Pt(IV) complexes; the huge reactivity difference orchestrates closely with the fact that the nucleophilicity of thiolate is much higher than the corresponding thiol. Hence, the attack of the sulfur atom in thiol/thiolate of Tiopronin on the axially-coordinated chloride in the Pt(IV) complexes is nucleophilic in nature in the rate-determining steps, resulting in a bridge formation and a subsequent bridged electron-transfer.
Studies of the inhibitory activities of Tiopronin and mercaptosuccinic acid on glutathione peroxidase and their cytotoxic and antioxidant properties
Pharmazie 2019 Sep 1;74(9):536-542.PMID:31484593DOI:10.1691/ph.2019.9472.
Glutathione peroxidase (GPx), an important antioxidative enzmye, can be inhibited by various thiols, including of Tiopronin and mercaptosuccinic acid (MSA). Recently, there has been discussion regarding the combination of Tiopronin in anticancer therapy to overcome acquired resistance to anticancer drugs. However, thiols are also known to act as antioxidants, which can be contraindicated in cancer chemotherapy. This article focuses on the inhibitory effects of Tiopronin and MSA on bovine and human glutathione peroxidase activities, and their effects on the redox status of cancer cells. IC50 values for the inhibition for the bovine erythrocyte enzyme were 356 and 24.7 μM for Tiopronin and MSA, respectively, with the corresponding Ki values of 343 μM and 14.6 μM, respectively at pH 7.4 and 25 °C. MSA inhibited human GPx activity in human cancer cell lysates at its IC50 while Tiopronin did not. Both compounds were cytotoxic to human cancer cell lines GUMBUS and HL-60, with IC50 values between 42.7 and 149.4 μM. Neither had an effect on cell cycle. Only MSA induced apoptosis in HL-60 cells but not in GUMBUS cells, while Tiopronin resulted in no apoptosis in either cell line. Combination studies of the MSA with hydrogen peroxide in living cells enhanced the production of reactive oxygen species in GUMBUS cells while Tiopronin acted as antioxidant in HL-60 cells. MSA and Tiopronin antagonized the cytotoxic effect of cisplatin, doxorubicin and methotrexate in combination studies. Our findings indicate that the antioxidant properties of both thiols prevail over their GPx inhibitory activity in human cancer cell lines.